Metabolomic Profiles in Patients with Cervical Cancer Undergoing Cisplatin and Radiation Therapy.

This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q ExactiveTM Focus Hybrid Quadrupole-OrbitrapTM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 µm) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40°C. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.

Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration.

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

Pharmacokinetics and bioequivalence of tofacitinib 5 mg in healthy Korean male subjects.

OBJECTIVE: Tofacitinib is an oral Janus kinase (JAK) inhibitor marketed as an immunomodulator that can effectively treat rheumatoid arthritis. This study aimed to compare the pharmacokinetics and evaluate the bioequivalence of tofacitinib free base (CKD-374) with those of tofacitinib citrate (Xeljanz). MATERIALS AND METHODS: A randomized, open-label, single-dose, 2-sequence, 2-period crossover study was conducted in healthy Korean male subjects. A total of 36 subjects were randomized into two sequence groups. At each period, subjects were administered the test formulation (tofacitinib free base, 5 mg) or the reference formulation (tofacitinib citrate, 8.078 mg; as tofacitinib, 5 mg). The plasma samples were collected up to 12 hours post dose and analyzed by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the plasma concentration vs. time curve from dosing to the last measurable concentration (AUC0-t), were determined by non-compartmental analysis. The 90% confidence intervals (CIs) of the geometric mean ratios for Cmax and AUC0-t were calculated to evaluate pharmacokinetic equivalence. RESULTS: The 90% CIs of the geometric mean ratios of Cmax and AUC0-t for tofacitinib free base to tofacitinib citrate were 0.9144 - 1.1230 and 1.0245 - 1.0932, respectively. All reported adverse events were of mild intensity, and there were no serious adverse events. CONCLUSION: In healthy Korean male adult subjects, the pharmacokinetic parameters of tofacitinib free base and tofacitinib citrate were evaluated and met the pharmacokinetic bioequivalent criteria. Both formulations were safe and well-tolerated.

Preoperative incongruent subtalar joint predicts less favorable clinical outcome in total ankle arthroplasty.

BACKGROUND: This study aimed to determine the clinical effect of incongruent subtalar joint space on total ankle arthroplasty (TAA). METHODS: Thirty-four consecutive patients who underwent TAA were grouped according to the status of subtalar joint incongruency. A comparison of clinical and radiographic parameters between groups as well as multiple regression analysis was performed to identify contributing factors to the final functional outcome. RESULTS: The final American Orthopaedic Foot and Ankle Society (AOFAS) score was significantly higher in the congruent group compared to that of the incongruent group (p = 0.007). There were no significant differences between the two groups in measured radiographic angles. In multiple regression analysis, the female sex (p = 0.006) and incongruency of the subtalar joint (p = 0.013) were found to be significant contributing factors to the final AOFAS score. CONCLUSIONS: A thorough preoperative investigation should be taken into the state of the subtalar joint for TAA.

Development of an External Control Arm Using Electronic Health Record-Based Real-World Data to Evaluate the Efficacy of COVID-19 Treatment.

To protect people from severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, tremendous research efforts have been made toward coronavirus disease 19 (COVID-19) treatment development. Externally controlled trials (ECTs) may help reduce their development time. To evaluate whether ECT using real-world data (RWD) of patients with COVID-19 is feasible enough to be used for regulatory decision making, we built an external control arm (ECA) based on RWD as a control arm of a previously conducted randomized controlled trial (RCT), and compared it to the control arm of the RCT. The electronic health record (EHR)-based COVID-19 cohort dataset was used as RWD, and three Adaptive COVID-19 Treatment Trial (ACTT) datasets were used as RCTs. Among the RWD datasets, eligible patients were evaluated as a pool of external control subjects of the ACTT-1, ACTT-2, and ACTT-3 trials, respectively. The ECAs were built using propensity score matching, and the balance of age, sex, and baseline clinical status ordinal scale as covariates between the treatment arms of Asian patients in each ACTT and the pools of external control subjects was assessed before and after 1:1 matching. There was no statistically significant difference in time to recovery between ECAs and the control arms of each ACTT. Among the covariates, the baseline status ordinal score had the greatest influence on the building of ECA. This study demonstrates that ECA based on EHR data of COVID-19 patients could sufficiently replace the control arm of an RCT, and it is expected to help develop new treatments faster in emergency situations, such as the COVID-19 pandemic.

Comparative pharmacokinetics of two formulations of 2.5-mg rivaroxaban in healthy Korean subjects.

OBJECTIVE: Rivaroxaban is a direct factor Xa inhibitor used for the prevention and treatment of thromboembolic disorders. The objective of this study was to compare the pharmacokinetic profiles of two rivaroxaban formulations after a single dose of rivaroxaban (2.5-mg tablet) in healthy Korean subjects. MATERIALS AND METHODS: This study was a randomized, open-label, single-dose, two-period, crossover study that included 34 healthy adult subjects under fasting conditions. The test drug (Yuhan rivaroxaban tablet) or reference drug (Xarelto tablet) was administered in each period. Serial blood samples were collected up to 36 hours post-dose. Plasma concentrations were measured by LC-MS/MS. Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable concentration (AUCt), were determined by non-compartmental analysis. The 90% confidence intervals (CIs) for the ratio of the geometric means of Cmax and AUCt for the test drug/reference drug were calculated to evaluate pharmacokinetic equivalence. RESULTS: A total of 28 subjects were included in the pharmacokinetic analysis. The geometric mean ratios (90% CI) of the test drug/reference drug for rivaroxaban were 1.0140 (0.9794 - 1.0499) for AUCt and 0.9350 (0.8797 - 0.9939) for Cmax. All adverse events (AEs) were mild, and there was no significant difference in the incidence of AEs between the formulations. CONCLUSION: The pharmacokinetic parameters of rivaroxaban were compared between the test and reference drug, and both formulations were bioequivalent. The newly developed rivaroxaban tablet is safe and well tolerated as the reference drug (ClinicalTrials.gov identifiers: NCT05418803).

Long-term taxonomic and functional stability of the gut microbiome from human fecal samples.

Appropriate storage of fecal samples is a critical step for unbiased analysis in human microbiome studies. The purpose of this study was to evaluate the stability of the fecal microbial community for up to 18 months. Ten healthy volunteers provided fecal samples at the Jeonbuk National University Hospital. Stool samples were stored under the following six conditions: four different storage temperatures (- 70 °C, - 20 °C, 4 °C, and room temperature [20-25 °C]) and two different collection tubes (OMNIgene-Gut and DNA/RNA shield-fecal collection tubes). The gut microbiome was analyzed with 16S rRNA sequencing. We compared the taxonomic composition, alpha diversity, beta diversity and inferred pathway abundance between the baseline and 18 months after storage. Samples collected in the DNA/RNA Shield-fecal collection tubes showed the best performance in preservation of the taxonomic composition at 18 months. Pairwise differences in alpha diversity metrics showed the least deviation from zero. The PERMANOVA test showed non-significant change of beta diversity metrics (Unweighted Unifrac: q-value 0.268; Weighted Unifrac: q-value 0.848). The functional stability was significantly well preserved in the DNA/RNA Shield-fecal collection tubes (adjusted p value < 0.05). Our results demonstrate the use of the DNA/RNA Shield-fecal collection tube as an alternative storage method for fecal samples to preserve the taxonomic and functional stability of the microbiome over a long term.

Injury-mechanism directness as a key factor for fracture laterality in pediatric extremity fractures.

BACKGROUND: Associations between certain extremity fracture sites and laterality in pediatric trauma are well known, whereas the rationale for such laterality tendencies are unclear. We hypothesized that the laterality tendency of a specific fracture would be affected by directness of injury mechanism and not by the fracture site itself. METHODS: We retrospectively enrolled 1382 children (aged 2-16 years) who were diagnosed with extremity fractures sustained during loss-of-balance situations and investigated the laterality tendencies (dominant vs. non-dominant extremity) of specific fracture sites. Multivariate analyses were sequentially performed to adjust for potential confounding variables-with and without injury-mechanism directness as a covariate. RESULTS: In the upper extremities, the non-dominant side was more prone to fractures (p < 0.001), especially of the distal supracondylar humerus, radial and/or ulnar shaft, and distal radius. In the lower extremities, the dominant side was more frequently fractured (p < 0.001), especially at the tibial shaft and distal tibia. However, the predisposing effects of specific fracture sites on fracture laterality were not statistically significant when in analysis adjusted for injury-mechanism directness as a covariate. Fracture laterality was affected by whether the injury mechanism was direct or indirect. Indirect injury to the upper extremity was strongly associated with non-dominant arm injury (odds ratio 0.686 [95% CI 0.517-0.991]; p = 0.009), whereas indirect injury to the lower extremity was strongly associated with dominant leg injury (odds ratio 2.138 [95% CI 1.444-3.165]; p < 0.001). CONCLUSIONS: Injury-mechanism directness, rather than fracture site itself, is a key factor that affects fracture laterality in pediatric extremity fractures. These findings are helpful for improving our understanding of which factors may affect fracture laterality among children.

Computer-Aided Diagnosis for Determining Sagittal Spinal Curvatures Using Deep Learning and Radiography.

Analyzing spinal curvatures manually is time-consuming and tedious for clinicians, and intra-observer and inter-observer variability can affect manual measurements. In this study, we developed and evaluated the performance of an automated deep learning-based computer-aided diagnosis (CAD) tool for measuring the sagittal alignment of the spine from X-ray images. The CAD system proposed here performs two functions: deep learning-based lateral spine segmentation and automatic analysis of thoracic kyphosis and lumbar lordosis angles. We utilized 322 datasets with data augmentation for learning and fivefold cross-validation. The segmentation model was based on U-Net, which has multiple applications in medical image processing. Here, we utilized parameter equations and trigonometric functions to design spinal angle measurement algorithms. The kyphosis (T4-T12) and lordosis angle (L1-S1, L1-L5) were automatically measured to help diagnose kyphosis and lordosis. The segmentation model had precision, sensitivity, and dice similarity coefficient values of 90.53 ± 4.61%, 89.53 ± 1.8%, and 90.22 ± 0.62%, respectively. The performance of the CAD algorithm was also verified with the Pearson correlation, Bland-Altman, and intra-class correlation coefficient (ICC) analysis. The proposed angle measurement algorithm exhibited high similarity and reliability during verification. Therefore, CAD can help clinicians in reaching a diagnosis by analyzing the sagittal spinal curvatures while reducing observer-based variability and the required time or effort.

Analysis of critical report notification from musculoskeletal radiology in a tertiary academic medical institution with a regional trauma center.

PURPOSE: We aimed to analyze the prevalence, causes, and clinical settings of 4-year critical radiologic reports (CRRs) notified from the musculoskeletal section of the radiology department. Then, we investigated the communication outcomes. METHODS: This study was approved by our institutional review board. We retrospectively included 175 musculoskeletal CRRs from our database between January 2017 and December 2020. The CRRs were analyzed by two musculoskeletal radiologists, who categorized the CRRs by clinical setting (emergency department(ED) patient, outpatient, and inpatient), body part, type of image modality, reason for CRR, incidental lesion, and clinical outcome. The clinical outcome was retrieved from the electronic medical records. RESULTS: The 175 musculoskeletal CRRs accounted for 5.4% of the CRRs (n = 3217) available in the study period. Most CRRs (94.9%, 166/175) corresponded to the musculoskeletal system, while the remaining ones (5.1%, 9/175) corresponded to the non-musculoskeletal system. In addition, the spine, extremities, and thoracic cage accounted for 52.6%, 40.6%, and 1.7% of the musculoskeletal CRRs, respectively. Moreover, most patients presented to the ED (50.3%, 88/175), followed by inpatients (30.9%, 54/175), and outpatients (18.9%, 33/175). The CRR reasons included missed fracture (54.3%), suspected malignancy (16%), clinical emergency (10.3%), unexpected infection/inflammation (11.4%), and others (8%). Furthermore, 11 (6.3%) incidental lesions were not related to the primary imaging purpose. Referring clinicians actively acknowledged 80% of the CRRs. The loss to follow-up action was the highest in the ED patients (35.2%, 31/88; p < 0.001), being significantly higher than that in outpatients (6.1%, 2/33) and inpatients (3.7%, 2/54). CONCLUSION: Missed fractures were the most common cause of musculoskeletal CRRs. ED showed prevalence in musculoskeletal CRRs and reflected the highest loss to follow-up action. ED physicians should pay more attention to CRRs to enhance patient care.

Pharmacokinetic properties and bioequivalence of gefitinib 250 mg in healthy Korean male subjects.

Gefitinib is an anti-cancer drug used to treat non-small cell lung cancer. The objective of this study was to compare the pharmacokinetics and evaluate the bioequivalence of 2 orally administered gefitinib 250 mg tablets in healthy Korean subjects. A randomized, open-label, single-dose, crossover bioequivalence study was conducted. A total of 50 healthy male volunteers were randomized into 2 sequence groups. During each treatment, the subjects received the test or reference formulation of 250 mg gefitinib with a washout period of 21 days. The plasma samples were collected at pre-dose and up to 144 hours post-dose, and plasma drug concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated, and the formulations were considered as bioequivalent if the 90% confidence intervals (CIs) of the geometric mean ratios were within the bioequivalence limits of 0.8 to 1.25. Forty-one subjects completed the study and were included in the pharmacokinetic analysis. The 90% CIs of the geometric mean ratios of the test formulation to the reference formulation were 0.8115 to 0.9993 for maximum plasma concentration and 0.9119 to 1.0411 for area under the plasma concentration versus time curve from dosing to the last measurable concentration. There were no serious or unexpected adverse events during the study. In healthy Korean adult subjects, the test and reference formulations of gefitinib 250 mg had similar pharmacokinetic parameters and similar plasma concentration-time profiles. The test formulation of gefitinib met the regulatory criteria for assuming bioequivalence. Both formulations were safe and well-tolerated.

Physeal Abnormalities in Children With High-risk Neuroblastoma Intensively Treated With/Without 13-Cis-Retinoic Acid.

BACKGROUND: This study aimed to investigate the presence of physeal abnormality and its effect on growth in children with high-risk neuroblastoma treated by intensive multimodal treatment with/without 13-cis-retinoic acid (13-CRA). METHODS: Fifteen patients diagnosed with high-risk neuroblastomas at the age of 1 to 10 years, who received treatment such as high-dose chemotherapy and autologous stem cell transplantation with/without 13-CRA, and with complete data during their >2-year follow-up were retrospectively reviewed. The physeal abnormalities were investigated by whole-body magnetic resonance imaging, serially performed every 3 to 6 months. The patients' height growth was also investigated and compared with that of age-and-sex-matched patients with brain tumors who also underwent high-dose chemotherapy and autologous stem cell transplantation. RESULTS: Six of 15 patients presented multifocal physeal abnormalities during follow-up, and all lesions occurred in patients with 13-CRA use. The lesions in 3 patients completely resolved spontaneously without any adverse effect on growth, but some lesions in the other 3 patients progressed to disturb the bony growth. Height growth of matched patients with brain tumors were not significantly different, and none of the matched controls showed definite bony deformity during the follow-up. CONCLUSIONS: Some children who were treated for high-risk neuroblastomas experienced multifocal physeal insults, probably due to the use of 13-CRA. Most lesions resolved spontaneously, but some led to bony deformity. If the lesions are not followed by premature physeal closure, there seems to be no further adverse effect of 13-CRA on leg length growth. Routine periodic screening for physeal status is needed for the patients with high-risk neuroblastomas using 13-CRA. LEVEL OF EVIDENCE: Level IV-prognostic study.

Pharmacokinetics of a New, Once-Daily, Sustained-release Pregabalin Tablet in Healthy Male Volunteers.

PURPOSE: A new sustained-release (SR) pregabalin formulation (YHD1119) designed for once-daily dosing has recently been developed to improve patient adherence. This study aimed to compare the pharmacokinetics of pregabalin SR and immediate-release (IR) formulations after multiple oral doses and to assess the effect of food on the pharmacokinetic profile of the pregabalin SR formulation after a single dose in healthy individuals. METHODS: Two clinical trials were conducted: a randomized, open-label, multiple-dose, 2-treatment, 2-period crossover study to evaluate the steady-state pharmacokinetic properties of SR treatment (pregabalin SR 300 mg once daily for 3 days) and IR treatment (pregabalin IR 150 mg twice daily for 3 days) under fed conditions and a randomized, open-label, single-dose, 2-treatment, 2-period, crossover study to evaluate the effect of food intake on the pharmacokinetic properties of the pregabalin SR formulation. Plasma concentrations of pregabalin were measured using LC-MS/MS. The AUC and Cmax for pregabalin were calculated using noncompartmental method and compared between treatments in each study. FINDINGS: Thirty-one individuals in the bioequivalence study and 23 in the food effect study completed the pharmacokinetic sampling. The geometric mean ratios of Cmax,ss and AUC0-τ between the SR and IR formulations were 1.1642 (90% CI, 1.1043-1.2272) and 0.9704 (90% CI, 0.9372-1.0047), respectively. The geometric mean ratios of Cmax and AUC0-last between the SR formulation in the fed state and in the fasted state were 1.6514 (90% CI, 1.3820-1.9732) and 1.7899 (90%CI, 1.4499-2.2097), respectively. IMPLICATIONS: The bioavailability of the pregabalin SR 300 mg formulation is increased if taken with a high-fat meal. Once-daily pregabalin SR 300 mg is bioequivalent to twice-daily pregabalin IR 150 mg under fed conditions at steady state. The pregabalin SR formulation is expected to improve patient adherence. ClinicalTrials.gov identifiers: NCT02783183 (bioequivalence study) and NCT03191136 (food effect study).

Automated Vertebral Segmentation and Measurement of Vertebral Compression Ratio Based on Deep Learning in X-Ray Images.

Vertebral compression fracture is a deformity of vertebral bodies found on lateral spine images. To diagnose vertebral compression fracture, accurate measurement of vertebral compression ratio is required. Therefore, rapid and accurate segmentation of vertebra is important for measuring the vertebral compression ratio. In this study, we used 339 data of lateral thoracic and lumbar vertebra images for training and testing a deep learning model for segmentation. The result of segmentation by the model was compared with the manual measurement, which is performed by a specialist. As a result, the average sensitivity of the dataset was 0.937, specificity was 0.995, accuracy was 0.992, and dice similarity coefficient was 0.929, area under the curve of receiver operating characteristic curve was 0.987, and the precision recall curve was 0.916. The result of correlation analysis shows no statistical difference between the manually measured vertebral compression ratio and the vertebral compression ratio using the data segmented by the model in which the correlation coefficient was 0.929. In addition, the Bland-Altman plot shows good equivalence in which VCR values are in the area within average ± 1.96. In conclusion, vertebra segmentation based on deep learning is expected to be helpful for the measurement of vertebral compression ratio.

A deep learning algorithm for automated measurement of vertebral body compression from X-ray images.

The vertebral compression is a significant factor for determining the prognosis of osteoporotic vertebral compression fractures and is generally measured manually by specialists. The consequent misdiagnosis or delayed diagnosis can be fatal for patients. In this study, we trained and evaluated the performance of a vertebral body segmentation model and a vertebral compression measurement model based on convolutional neural networks. For vertebral body segmentation, we used a recurrent residual U-Net model, with an average sensitivity of 0.934 (± 0.086), an average specificity of 0.997 (± 0.002), an average accuracy of 0.987 (± 0.005), and an average dice similarity coefficient of 0.923 (± 0.073). We then generated 1134 data points on the images of three vertebral bodies by labeling each segment of the segmented vertebral body. These were used in the vertebral compression measurement model based on linear regression and multi-scale residual dilated blocks. The model yielded an average mean absolute error of 2.637 (± 1.872) (%), an average mean square error of 13.985 (± 24.107) (%), and an average root mean square error of 3.739 (± 2.187) (%) in fractured vertebral body data. The proposed algorithm has significant potential for aiding the diagnosis of vertebral compression fractures.

Prognostic significance of radiodensity-based skeletal muscle quantification using preoperative CT in resected non-small cell lung cancer.

BACKGROUND: Sarcopenia is associated with poor prognosis in lung cancer. Skeletal muscle area can be quantified based on radiodensity of CT scan. The purpose of this study was to evaluate the prognostic significance of radiodensity-based detailed skeletal muscle quantification on outcomes after surgery of non-small cell lung cancer (NSCLC). METHODS: Single cross-sectional area of the skeletal muscle (-29 to 150 HU) at the 3rd lumbar vertebra (L3) level retrospectively measured on preoperative CT for NSCLC patients (n=272), who underwent surgical resection during 2011 to 2016. The diagnosis of sarcopenia was made when a L3 muscle index (L3MI; L3 muscle area/height2) of less than 55 cm2/m2 for men and less than 39 cm2/m2 for women. Skeletal muscle was subsequently classified based on radiodensity level as low attenuation muscle (-29 to <30 HU) and high attenuation muscle (30 to 150 HU). Using a maximal-chi-squared test, low attenuation muscle accounted less than 24.5% of the total muscle, which was considered healthy muscle. Data on clinical characteristics (demographic information, TNM stage, histology) and prognosis (disease-free survival; DFS, and overall survival; OS) were collected. RESULTS: Sarcopenia was found 22.4% in preoperative CT (32.9% for men and 6.5% for women). The prevalence of patients with healthy muscle was 15.4% (21.3% for men and 6.5% for women). There was no significant difference between the 3-year DFS rate (77.0% vs. 67.0%, P=0.142) or 3-year OS rate (84.8% vs. 87.9%, P=0.576) between patients with and without sarcopenia. However, patients with healthy muscle tend to show longer 3-year DFS rate (79.4% vs. 67.2%, P=0.094) and 3-year OS rate (92.6% vs. 86.1%, P=0.176). In the multivariable analysis, healthy muscle was one of the independent prognosticators for a 3-year DFS rate (HR, 0.50, P=0.035), along with R1 resection (HR, 5.90, P<0.001), pathologic T stage (HR, 2.69, P<0.001), and pathologic N stage (HR, 2.43, P<0.001). CONCLUSIONS: The proportion of low attenuation muscle was associated with DFS in resected lung cancer patients. Further investigation is needed to establish whether radiodensity-based detailed skeletal muscle quantification could be early biomarker to predict prognosis in NSCLC.

Triaging deep vein thrombosis using ultrasonography after lower-extremity orthopedic surgery: analysis of a single-center experience.

PURPOSE: This study aimed to stratify risk factors and vein levels for postoperative deep vein thrombosis (DVT) after lower-extremity orthopedic surgery. METHODS: Ninety-nine patients who underwent Doppler ultrasonography after lower-extremity orthopedic surgery were enrolled. Medical records were reviewed for anesthesia duration, type of surgery, body weight, height, and cardiovascular risk factors (including history of smoking, diabetes mellitus or hypertension, blood pressure, and total cholesterol and high-density lipoprotein [HDL] cholesterol levels), and the DVT treatment. Ultrasound diagnosis of DVT was made according to a routine protocol. The relationships between selected factors and the presence of DVT were assessed using univariate and multivariate regression analyses. RESULTS: Thirty-three (33%) patients were found to have calf DVT. The mean age, weight, and height of the non-DVT and postoperative DVT patients were 55.1 years versus 65.4 years, 70.5 kg versus 61.2 kg, and 163.3 cm versus 157.0 cm, respectively. Total cholesterol/HDL levels in the non-DVT and DVT patients were 70.6/20.7 mg/dL and 90.8/26.0 mg/dL, retrospectively. Systolic and diastolic blood pressure in the non-DVT and DVT patients were 133.6/80.2 mm Hg and 132.2/78.1 mmHg, respectively. The mean duration of anesthesia was 173.9 versus 199.9 minutes, and the operative time was 136.4 minutes versus 161.0 minutes. Older age (P=0.005) and lower body weight (P=0.002) were significantly associated with postoperative DVT. No other significant between-group differences were found (P>0.05). The patients with ultrasound-identified DVT received antithrombotic treatment. None of them had distant thromboembolism. CONCLUSION: After lower-extremity orthopedic surgery, the calf veins in elderly patients with low body weight are susceptible to thrombosis; they would most likely benefit from postoperative ultrasonography.

Pharmacokinetic Interactions between Tegoprazan and Metronidazole/Tetracycline/Bismuth and Safety Assessment in Healthy Korean Male Subjects.

PURPOSE: Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this study was to evaluate the pharmacokinetic interaction between tegoprazan and triple-antibiotic therapy containing metronidazole, tetracycline, and bismuth. METHODS: An open-label, 2-cohort, randomized, multiple-dose, crossover study was conducted in healthy subjects. In cohort 1, tegoprazan (100 mg/d) was administered orally with or without triple-antibiotic therapy (1500 mg/d metronidazole, 2000 mg/d tetracycline, and 1200 mg/d bismuth) for 7 days in each period. In cohort 2, triple-antibiotic therapy was administered orally with or without tegoprazan for 7 days in each period. Pharmacokinetic blood samples were collected within 24 h after the last dose. Safety assessments were performed. FINDINGS: Eleven cohort 1 subjects and ten cohort 2 subjects were included in the pharmacokinetic analysis. The AUCτ and Cmax at steady state geometric mean ratios (90% CIs) were 0.78 (0.73-0.83) and 0.75 (0.68-0.82) for tegoprazan; 0.77 (0.68-0.88) and 0.84 (0.72-0.98) for tegoprazan metabolite M1; 1.03 (0.98-1.08) and 1.08 (0.99-1.18) for metronidazole; 0.63 (0.56-0.70) and 0.64 (0.56-0.74) for tetracycline; and 1.55 (0.99-2.44) and 1.38 (0.72-2.66) for bismuth, respectively. All reported adverse events were mild. IMPLICATIONS: Changes in the tegoprazan, tetracycline, and bismuth pharmacokinetic parameters were detected after concurrent administration. These changes were considered mainly due to the pharmacodynamic effect of tegoprazan. The adverse events were predictable and reported as frequent adverse events during triple-antibiotic therapy. There were no significant differences in safety or tolerability between quadruple therapy, including tegoprazan and triple-antibiotic therapy. ClinicalTrials.gov identifier: NCT04066257.